Neuropathology remains a useful discipline, especially in characterization of neurodegenerative diseases. In fact, it provides the "gold-standard" for diagnosis of non-Alzheimer neurodegenerative diseases, including progressive supranuclear palsy, corticobasal degeneration and the frontotemporal dementias. The broad goal of the Neuropathology Core (NP Core) is to provide neuropathologic characterization of brains of humans and animal models that are engineered in research projects that focus on the role of tau protein in neurodegeneration. In particular, the NP Core will characterize and provide postmortem tissue for genetic studies, provide electron microscopic and confocal microscopic services, and process animal brains with a complement of histopathologic methods. Among the specific activities of the NP Core are the following: 1. Perform neuropathologic evaluation of human and animal brains using standardized methods for collection and banking of fresh and fixed brain tissue; standard gross dissection and tissue sampling; histopathologic analysis with routine histological methods as well as fluorescent microscopy, immunocytochemistry, laser confocal microscopy, image analysis and electron microscopy. 2. Conduct gross and microscopic clinicopathologic conferences for discussion of cases relevant to this application. 3. Characterize brains of humans and animals with immunocytochemistry and a panel of antibodies to tau protein, as well as antibodies to phosphorylated and non-phosphorylated neurofilament, ubiquitin, alpha-synuclein, synaptophysin, glial fibrillary acidic protein and class II major histocompatibility antigen. 4.Embed and section tissue culture specimens for electron service for confocal microscopy of tissue and cultured cells. 6. Provide image analysis of animal brains to provide a measure of neuronal loss. 7. Maintain a database of pathologic parameters for cases and controls. In its functions of NP Core serves a link between the basic science projects of this grant and clinical studies of a group of uncommon, but related, neurodegenerative disorders.